Nasrollahzadeh Javad, Siassi Fereydoun, Doosti Mahmood, Eshraghian Mohammad Reza
Department of Human Nutrition, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Exp Ther Oncol. 2009;8(2):95-103.
Docosahexaenoic acid (DHA) may have potential anticarcinogenic effect. In the present study, effect of DHA on rat C6 glioma was tested. In vitro, cytotoxic effect of 50-400 microM DHA on C6 cells was evaluated and compared with linoleic acid (LA). In vivo, adult female Wistar rats implanted with C6 tumor, fed 1 ml of DHA oil (containing 73% DHA, 36 rats) or LA oil (containing 72-77% LA, 41 rats) daily, starting one week prior to tumor implantation until death or if survived, until 30 days after implantation. Another group of tumor bearing rats was treated with chloroethyl-cyclohexyl-nitrosourea (CCNU, 30 mg/kg, 31 rats) at day 8 post implantation to show if the result of oil supplementation is comparable to single agent chemotherapy. mRNA expression of p21 and p27 was determined in vitro at 100 and 150 microM of fatty acids and in tumors of rats supplemented with LA or DHA oils. In vitro, DHA, but not LA, had cytotoxic effect on C6 cells at 200 and 400 microM and DHA increased mRNA expression of p21 at 150 microM (p < 0.05). In rat glioma model, although a non-significant trend towards better survival was observed in DHA oil relative to LA oil group, the difference was not significant (p = 0.20). p21 and p27 mRNA expression in tumors of DHA oil group did not differ with LA oil group. Single dose of CCNU increased survival when compared to LA oil group (p < 0.001). In conclusion, intake of DHA at the dose or duration employed in the present study might be insufficient to bring about its cytotoxic action on rat's C6 brain tumor.
二十二碳六烯酸（DHA）可能具有潜在的抗癌作用。在本研究中，测试了DHA对大鼠C6胶质瘤的影响。在体外，评估了50 - 400微摩尔DHA对C6细胞的细胞毒性作用，并与亚油酸（LA）进行比较。在体内，成年雌性Wistar大鼠植入C6肿瘤后，从肿瘤植入前一周开始每天喂食1毫升DHA油（含73%DHA，36只大鼠）或LA油（含72 - 77%LA，41只大鼠），直至死亡，若存活则直至植入后30天。另一组荷瘤大鼠在植入后第8天用氯乙环己基亚硝脲（CCNU，30毫克/千克，31只大鼠）治疗，以表明补充油的结果是否与单药化疗相当。在体外，于100和150微摩尔脂肪酸浓度下以及在补充LA或DHA油的大鼠肿瘤中测定p21和p27的mRNA表达。在体外，200和400微摩尔的DHA对C6细胞有细胞毒性作用，而LA无此作用，且150微摩尔的DHA可增加p21的mRNA表达（p < 0.05）。在大鼠胶质瘤模型中，尽管相对于LA油组，DHA油组观察到有更好生存的非显著趋势，但差异不显著（p = 0.20）。DHA油组肿瘤中的p21和p27 mRNA表达与LA油组无差异。与LA油组相比，单剂量CCNU可提高生存率（p < 0.001）。总之，在本研究中采用的剂量或持续时间摄入DHA可能不足以对大鼠C6脑肿瘤产生细胞毒性作用。
